Atrial fibrillation (AF) is a common arrhythmia and is assuming increased public health importance as the population ages. The overall objective of this project is to identify novel risk factors for the development of incident AF and to evaluate its natural history and thrombotic complications. Thrombosis, and in particular ischemic stroke, is the most devastating complication of AF, and is a leading cause of death and disability in patients with AF. Knowledge about the risk of stroke in patients with transitory AF (a single episode of AF or AF lasting 7 days or less) is limited. Information is needed to guide anticoagulation decisions for patients with transitory AF, particularly as novel antithrombotic agents are developed. The proposed renewal project will investigate the prognosis of AF in an inception cohort of AF patients at Group Health. Among approximately 750 patients with transitory AF, risk factors will be studied for progression to paroxysmal and permanent AF. Stroke risk in patients with transitory AF will be compared to risk in those with no AF. With the recognition that AF occurs with increased frequency among members of the same family, a genetic contribution to AF risk is likely. Genome-wide association studies of AF are under way. Data from AF cases and controls in the Group Health study will be used to replicate findings from ongoing genome-wide association studies of AF. In addition, this project will identify patients with early-onset AF, defined as AF occurring in a person 65 years of age or younger and without underlying structural heart disease. There are few contemporary epidemiologic studies of early-onset AF, and genetic predisposition to AF may be most easily detected among people without clinical cardiovascular disease as an etiologic factor. Genome-wide scans will be performed in newly-identified patients with early-onset AF, and results will be combined with those from other studies in a meta-analysis of genome-wide associations with early-onset AF. The ultimate goal of this research is to increase knowledge about AF risk factors and prognosis and to enhance prevention efforts and improve care for patients with AF.